(Supported by NIH GMS 40198 to C. L. Rieder). In this study laser microsurgery was used to determine when the RAD-9 checkpoint is turned off in vertebrate somatic cells. Studies in yeast reveal that mitosis is arrested when the chromosomes are damaged by irradiation. However, we know from work in our laboratory that vertebrate somatic cells do not respond the same way. Rather, in these cells mitosis proceeds normally when the chromosomes are severed by laser microsurgery after nuclear envelope breakdown. In the current study we examined the effect of localized damage to the DNA and cytoplasm in controlling nuclear envelope breakdown. We found that damaging DNA in mid-prophase cells returns them to interphase, but that the same experiment on late prophase cells does not inhibit entry into mitosis. We also found that the radiation induced reversion of prophase cells to interphase correlates with the dephosphorylation of histone H1, histone H3 and the MPM-2 epit opes. Th ese data are the first to demonstrate that the cell cycle is reversible, and suggest that this reversion is mediated by a down-regulation of CDK1 activity during mid-prophase. Rieder, C. L., A. Khodjakov and R.W. Cole. (1998) The radiation-induced reversal of the cell cycle during prophase: Implications for the checkpoint control of the G2/M transition in vertebrates. Chromosome Segregation and Aneuploidy 4th Internat. Workshop, Porto, Portugal, July 1-6. Rieder, C. L. and R.W. Cole (1998). Entry into mitosis in vertebrate somatic cells is guarded by a chromosome damage checkpoint that reverses the cell cycle when triggered during early but not late prophase. J. Cell Biolgy, 142:1-10.